Azole antifungals are a group of fungistatic agents that can be administered orally or parenterally. The determination of the concentrations of these antifungals (miconazole, fluconazole, ketoconazole ... [more ▼]

Azole antifungals are a group of fungistatic agents that can be administered orally or parenterally. The determination of the concentrations of these antifungals (miconazole, fluconazole, ketoconazole, posaconazole, voriconazole, itraconazole, and its major active metabolite, hydroxy-itraconazole) in serum can be useful to adapt the doses to pharmacological ranges because of large variability in the absorption and metabolism of the drugs, multiple drug interactions, but also potential resistance or toxicity. A method was developed and validated for the simultaneous determination of these drugs in serum utilizing ultra-high pressure liquid chromatography and diode array detection (UHPLC-DAD). After a simple and rapid liquid– liquid extraction, the pre-treated sample was analysed on an UHPLC-DAD system (Waters CorporationH). The chromatographic separation was carried out on an Acquity BEH C18 column (Waters Corporation) with a gradient mode of mobile phase composed of acetonitrile and aqueous ammonium bicarbonate 10.0 M pH10. The flow rate was 0.4 ml/min and the injection volume was 5 ml. The identification wavelength varied according to the drug from 210 to 260 nm. The method was validated by the total error method approach by using an analytical validation software (eNnoval V3.0 ArlendaH). The seven azole antifungals were identified by retention time and specific UV spectra, over a 13-minute run time. All calibration curves showed good linearity (r2.0.99) in ranges considered clinically adequate. The assay was linear from 0.05 to 10 mg/l for voriconazole, posaconazole, itraconazole, hydroxy-itraconazole, and ketoconazole, from 0.3 to 10 mg/l for fluconazole, and from 0.1 to 10 mg/l for miconazole. The bias and imprecision values for intraand inter-assays were lower than 10% and than 15%, respectively. In conclusion, a simple, sensitive, and selective UHPLC-DAD method was developed and validated to determine seven azole antifungal drugs in human serum. This method is applicable to patient samples, and can be applied successfully to clinical applications and therapeutic drug monitoring. [less ▲]

Biological monitoring, also called biomonitoring, is a process to prevent and assess health risk for individuals exposed to chemical products present in environment or through workplace exposure ... [more ▼]

Biological monitoring, also called biomonitoring, is a process to prevent and assess health risk for individuals exposed to chemical products present in environment or through workplace exposure. Biomonitoring is most often a monitoring of exposure or of effect. The exposure monitoring is currently the most widespread in toxicology. It involves the determination in biological fluids of different biomarkers, most of which are biomarkers of internal dose. These biological indicators are typically measured in blood and urine, but other biological samples can be analyzed. They are used to assess the penetration of environmental pollutants into the body. Assay results are interpreted in relation to reference values which are adapted either to occupationally exposed populations, or to general population. This interpretation and the choice of appropriate biomarker of exposure are not always obvious. Biomonitoring has some limitations despite its many advantages. It is complementary to another health prevention approach: the monitoring of ambient air. To illustrate in practice the biomonitoring of exposure, several examples of toxics and their associated biomarkers are reviewed: benzene, toluene, styrene, polycyclic aromatic hydrocarbons, chloroform, 2-hexanone and hydrogen cyanide. [less ▲]

PURPOSE: Nearly one billion people around the world are deficient in vitamin D and need to be supplemented. Vitamin D is available in medicines and fortified foods. It is available in two forms: vitamin ... [more ▼]

PURPOSE: Nearly one billion people around the world are deficient in vitamin D and need to be supplemented. Vitamin D is available in medicines and fortified foods. It is available in two forms: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). KEY POINTS: The pharmacopeiae consider these steroid hormones as equivalent and interchangeable. However, several studies have showed that serum level of 25(OH)D is increased more effectively with vitamin D3 than vitamin D2. Vitamin D2 has shorter plasma half-life and a lower affinity for the vitamin D binding protein, the hepatic vitamin D hydroxylase and the vitamin D receptor. CONCLUSION: Vitamin D2 should not be regarded anymore as suitable for supplementation or fortification. Currently though, it is still the most used in some countries such as Portugal and Australia. [less ▲]